Vitamin D ointment for prevention of radiation dermatitis in breast cancer patients.

Radiation dermatitis occurs frequently during adjuvant radiation therapy for breast cancer. Prevention of radiation dermatitis by applying various creams and ointments has a limited success, and Aqua cream which has urea as one of its active ingredients is used in many institutions as a preventive treatment. The primary goal of this study is to assess the effect of vitamin D (calcipotriol) ointment in prevention of radiodermatitis in breast cancer patients compared to Aqua cream.

TNF-α increases the expression and activity of vitamin D receptor in keratinocytes: role of c-Jun N-terminal kinase.

Several inflammatory mediators increase calcitriol production by epidermal keratinocytes. In turn calcitriol attenuates the keratinocyte inflammatory response. Since the effect of the in-situ generated calcitriol depends also on the sensitivity to the hormone we studied the effect of inflammatory cytokines on the response of HaCaT human keratinocytes to calcitriol by examining the expression and transcriptional activity of VDR.

Vitamin D Induces Cyclooxygenase 2 Dependent Prostaglandin E2 Synthesis in HaCaT Keratinocytes.

The active metabolite of vitamin D calcitriol and its analogs are well-known for their anti-inflammatory action in the skin, while their main side effect associated with topical treatment of inflammatory disorders is irritant contact dermatitis. Prostaglandin E2 (PGE2 ) is pro-inflammatory at the onset of inflammation and anti-inflammatory at its resolution. We hypothesized that induction of PGE2 synthesis by calcitriol in epidermal keratinocytes may contribute both to its pro-inflammatory and anti-inflammatory effects on the skin.

The inflammatory response of keratinocytes and its modulation by vitamin D: the role of MAPK signaling pathways.

The hormonal form of vitamin D, calcitriol, and its analogs are known for their beneficial effect in the treatment of inflammatory skin disorders. Keratinocytes play a role in epidermal inflammatory responses invoked by breeching of the epidermal barrier, by infectious agents and by infiltrating immune cells. We studied the role of calcitriol in the initiation of keratinocyte inflammatory response by the viral and injury mimic polyinosinic-polycytidylic acid (poly(I:C)) and in its maintenance by tumor-necrosis-factor α (TNFα) and investigated the role of the mitogen-activated protein kinase cascades in these processes and their regulation by calcitriol.

Popeye domain-containing 1 is down-regulated in failing human hearts.

Congestive heart failure, a complex disease of heterogeneous etiology, involves alterations in the expression of multiple genes. The Popeye domain-containing (POPDC) family of three novel muscle-restricted genes (POPDC1-3) is evolutionarily conserved and developmentally regulated. In mice, POPDC1 has been shown to play an important role in skeletal and cardiac muscles subjected to injury or stress.

Upregulation of MMP-9 production by TNFalpha in keratinocytes and its attenuation by vitamin D.

MMP-9, a member of the matrix metalloproteinase family that degrades collagen IV and processes chemokines and cytokines, participates in epidermal remodeling in response to stress and injury. Limited activity of MMP-9 is essential while excessive activity is deleterious to the healing process. Tumor necrosis factor (TNFalpha), a key mediator of cutaneous inflammation, is a powerful inducer of MMP-9.

Vitamin D protects keratinocytes from deleterious effects of ionizing radiation.

Background: Radiotherapy can induce severe skin responses that may limit the clinically acceptable radiation dose. The responses include erythema, dry and moist desquamation, erosions and dermal-epidermal blister formation. These effects reflect injury to, and reproductive failure of, epidermal cells and may also be due to dysregulation of the tissue remodelling process caused by excessive proteolytic activity.

Two modes of ERK activation by TNF in keratinocytes: different cellular outcomes and bi-directional modulation by vitamin D.

Inflammation, elicited in the skin following tissue damage or pathogen invasion, may become chronic with deleterious consequences. Tumor necrosis factor (TNF) is a key mediator of cutaneous inflammation and the keratinocyte an important protagonist of skin immunity. Calcitriol, the hormonally active vitamin D metabolite, and its analogs attenuate epidermal inflammation and inhibit the hyperproliferation of keratinocytes associated with the inflammatory disorder, psoriasis.

The Popdc gene family in the rat: molecular cloning, characterization and expression analysis in the heart and cultured cardiomyocytes.

Three Popeye domain-containing (Popdc 1-3) family-members are known in vertebrates. Their exact function is as yet unknown although involvement in cell adhesion has been suggested. We report herein sequencing of the rat Popdc 1-3 cDNAs that show high homology to other vertebrate orthologs and are expressed primarily in the heart and skeletal muscles.

Calcitriol sensitizes colon cancer cells to H2O2-induced cytotoxicity while inhibiting caspase activation.

The anti-cancer activity of calcitriol, the active metabolite of Vitamin D, in the colon is usually attributed to its anti-proliferative and pro-differentiative actions. The levels of reactive oxygen species (ROS) are high in colon carcinomas due to increased aerobic metabolism and exposure to various anti-cancer modalities. We examined whether calcitriol modulates the response of colon cancer cells to the cytotoxic action of the common mediator of ROS injury, H2O2.

Programmed cell death of stressed keratinocytes and its inhibition by vitamin D: the role of death and survival signaling pathways.

The epidermis is confronted with multiple environmental and pathophysiological stresses. This study shows that TNFalpha, oxidative stress, hyperosmotic and heat shock induced both caspase-dependent and independent cell death in human HaCaT keratinocytes. The hormonal form of vitamin D, 1,25(OH)2D3, which is an autocrine hormone in the epidermis, protected the cells from all the examined stresses and pathways leading to cell death.

Expression of procollagen C-proteinase enhancer-1 in the remodeling rat heart is stimulated by aldosterone.

Excessive collagen deposition is a common complication of myocardial infarction that causes progressive heart disease. Several pro-fibrotic cytokines and hormones, including aldosterone, control this process. Procollagen processing by procollagen C-proteinase(s) is critical for collagen deposition and is potentiated by procollagen C-proteinase enhancer proteins (PCPEs).

Vitamin D sensitizes breast cancer cells to the action of H2O2: mitochondria as a convergence point in the death pathway.

Calcitriol, the hormonal form of vitamin D3, sensitizes breast cancer cells to reactive oxygen species (ROS)-dependent cytotoxicity induced by various anticancer modalities. This effect could be due to increased generation of ROS and/ or to increased sensitivity of the target cells to ROS. This work examined the effect of calcitriol on the damage inflicted on breast cancer cells by the direct action of ROS represented by H2O2.

Expression of procollagen C-proteinase enhancer in cultured rat heart fibroblasts: evidence for co-regulation with type I collagen.

Procollagen processing by procollagen C-proteinase (PCP) is an important step in collagen deposition. This reaction is stimulated by another glycoprotein, known as PCP enhancer. The objective of this study was to identify factors that regulate the expression of PCP enhancer in cardiac fibroblasts and examine possible correlation with collagen expression.

Vitamin D enhances mitogenesis mediated by keratinocyte growth factor receptor in keratinocytes.

The hormonally active vitamin D metabolite, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), and keratinocyte growth factor (KGF) belong to the network of autocrine and paracrine mediators in the skin. Both were shown to modulate keratinocyte proliferation, to reverse epidermal atrophy, to increase wound healing, and to reduce chemotherapy-induced alopecia. The overlap between their activities may suggest that vitamin D exerts some of its actions by modulation of KGF activities in the skin.

ANP expression in the hypertensive heart.

Atrial natriuretic peptide (ANP), the principal member of the natriuretic factor family of peptides, primarily a product of the atria in the adult heart, is also expressed in the fetal ventricles. A minority of ventricular impulse-conducting cells and myocytes exposed to extreme tension retain the capacity to produce ANP in the adult. The number and distribution of ANP-expressing cells increases dramatically when the ventricle is pressure loaded and hypertrophied, as in the case of chronic hypertension.

Vitamin D inhibits the activation of stress-activated protein kinases by physiological and environmental stresses in keratinocytes.

In addition to its known effects on keratinocyte proliferation and differentiation, the hormonal form of vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), has been shown to protect keratinocytes from UV- and chemotherapy-induced damage. Epidermal keratinocytes contain both the machinery needed to produce 1,25(OH)(2)D(3) and vitamin D receptors. The activation of the stress-activated protein kinases (SAPKs), such as c-Jun N-terminal kinase (JNK) and p38, is an early cellular response to stress signals and an important determinant of cell fate.

Association of tetralogy of Fallot with a distinct region of del22q11.2.

Congenital heart defects (CHDs) appear in greater frequency among relatives of patients and in individuals with DiGeorge syndrome (DGS) or velo-cardio-facial syndrome (VCFS). A majority of these patients and part of the apparently nonsyndromic CHD patients with conotruncal defects manifest hemizygous deletions within chromosome 22q11.2 (del22q11).

Vitamin D is a prooxidant in breast cancer cells.

The anticancer activity of the hormonal form of vitamin D, 1,25-dihydroxyvitamin D [1,25(OH)2D], is associated with inhibition of cell cycle progression, induction of differentiation, and apoptosis. In addition, 1,25(OH)2D3 augments the activity of anticancer agents that induce excessive reactive oxygen species generation in their target cells. This study aimed to find out whether 1,25(OH)2D3, acting as a single agent, is a prooxidant in cancer cells.

Occurrence and distribution of atrial natriuretic peptide-containing cells in the left ventricle of hypertensive rats. Effect of antihypertensive treatment.

In the ventricles of adult mammalian hearts, production of atrial natriuretic peptide (ANP) is negligible, restricted to the impulse-conducting cells, the papillary muscles, and a minority of subendocardial myocytes. ANP expression is reinduced in the ventricles of pressure-overloaded and failing hearts and is frequently used as a marker for myocyte hypertrophy. Using an immunohistochemical approach, we have characterized the size distribution of ANP-containing myocytes in the left ventricle of the spontaneously hypertensive rat (SHR) before and after chronic antihypertensive therapy and compared the results to age-matched normotensive Wistar rats (WR).

Uptake of pivaloyloxymethyl butyrate into leukemic cells and its intracellular esterase-catalyzed hydrolysis.

Unlabelled: Pivaloyloxymethyl butyrate (AN-9), a butyric acid (BA) prodrug, exhibited low toxicity and significant anticancer activity in vitro and in vivo. The purpose of this study was to elucidate the basis for AN-9 increased anticancer activity compared to BA, by studying the uptake of BA and AN-9 into the cells.

Methods: The uptake rate and level of [14C]-AN-9 and [14C]-BA, labeled on the carboxylic moiety of BA, into HL-60 and MEL leukemic cell lines was measured.

Synergistic anticancer activity of 1,25-dihydroxyvitamin D(3) and immune cytokines: the involvement of reactive oxygen species.

It was previously shown that 1,25-dihydroxyvitamin D(3) (1, 25(OH)(2)D(3)) enhances the cytotoxic activity of tumor necrosis factor alpha (TNFalpha), doxorubicin and menadione. A feature shared by these anticancer agents is the involvement of reactive oxygen species (ROS) in their action. In this work we found that 1, 25(OH)(2)D(3) acted synergistically with interleukin 1 beta (IL-1beta) or interleukin 6 (IL-6) to inhibit the proliferation of MCF-7 breast cancer cells.

The myocardial profile of the cytosolic isozymes of creatine kinase is apparently not related to cyanosis in congenital heart disease.

Background: CKMB, the cardiac-specific heterodimer of cytosolic creatine-kinase (CK), is developmentally and physiologically regulated, tissue hypoxia being a proposed regulator. In patients with cyanotic heart disease the myocardium is perfused with partially saturated blood. We questioned whether the myocardium of cyanotic subjects contains higher proportions of CKMB.

1,25-Dihydroxyvitamin D3 enhances the susceptibility of breast cancer cells to doxorubicin-induced oxidative damage.

1,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the hormonal form of vitamin D, has anticancer activity in vivo and in vitro. Doxorubicin exerts its cytotoxic effect on tumor cells mainly by two mechanisms: (a) generation of reactive oxygen species (ROS); and (b) inhibition of topoisomerase II. We studied the combined cytotoxic action of 1,25(OH)2D3 and doxorubicin on MCF-7 breast cancer cells.

Involvement of tumor necrosis factor alpha and interleukin-1beta in enhancement of pentylenetetrazole-induced seizures caused by Shigella dysenteriae.

Neurologic manifestations, mainly convulsions, are the most frequent extraintestinal complications of shigellosis. We used an animal model to study the roles of tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) in Shigella-related seizures. Administration of Shigella dysenteriae 60R sonicate enhanced the sensitivity of mice to the proconvulsant pentylenetetrazole (PTZ) within 7 h.